Abstract
Clavulanic acid (CA) is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus. The combination of clavulanic acid with amoxicillin is the most successful example of the use of traditional β-lactam antibiotics sensitive to β-lactamase together with β-lactamase inhibitor substances. In this study, the medium composition, operation conditions and kinetic behavior for production of CA by S. clavuligerus were investigated. The optimum composition was found to be the concentration of soybean meal extract is 40 g/l, 10 g/l NZ-amine, 20 g/l glycerol, 1 g/l KH2PO4, 1 g/l MgSO4．7H2O and the initial pH was adjusted to 7.0. The optimum pH and agitation rate was 7.5 and 500 rpm, respectively. When the strain was cultivated in this optimum medium composition and culture conditions, the maximum CA concentration was 339 mg/l. The positive effect was observed when the cultivation was fed with glycerol, CA production increased 2.2-flod compared with the cultivation without fed glycerol. And the decreased of the CA concentration was mainly due to decomposition or re-metabolisation of CA in the presence of the microorganism. The cell growth, CA production and the substrate utilization were found to be successfully expressed by the logistic model, the Luedeking-Piret model and modified Luedeking-Piret model, respectively. CA production followed both the growth-associated pattern and the non- growth-associated pattern. Furthermore, the effect of pH values on the kinetic parameters was also studied.